Human mammary epithelium is located within a network of branched ducts terminating in lobules, is surrounded by a basement membrane, and is embedded in fat and connective tissue. The epithelium of the mammary gland has been classically subdivided into two categories, i.e., luminal cells that border the lumen and basal cells also referred to as myoepithelial cells that are situated between the basement membrane and the luminal epithelium.
Myoepithelial cells are derived from ectoderm and are known to exhibit both epithelial and mesenchymal characteristics (Cutler and Chaundry (1973) J. Morphol., 140:343-354, and Franke et al. (1980) J. Cell, Biol., 84:633-654, both of which are incorporated herein by reference). They are situated between acinar or ductal luminal cells and the basal lamina in a number of secretory glands, such as breast, lacrimal, eccrine, and apocrine sweat glands and various salivary glands.
A major problem in studies of human mammary-gland differentiation both in vivo and in culture has been the lack of markers which allow a rapid, reproducible, and clear definition of the two epithelial subclasses. Similarly, a major problem in the accurate diagnosis of the malignancy of mammary and other epithelial neoplasms stems in part from this same lack of suitable markers.
For some tumors, marker typing often provides oncologists with crucial prognostic insights, which in turn dictates the most suitable treatment regimen. For example, while a nonagressive tumor may be surgically removed without significant risk of recurrence or metastasis, the removal of an aggressive tumor must be generally accompanied by the induction of drugs, isotopes or other chemotherapeutic agents to ensure cure. In addition to the expense of such aggressive treatments, the patient can experience very severe side-effects.
Although considerable advances have been made recently in the typing of some carcinomas (such as by immunocytochemical procedures), the severity of most remains uncertain until the disease has progressed. This is particularly true of mammary carcinomas, where even the commonly utilized estrogen and progesterone receptor assays cannot predict tumor invasiveness, recurrence or other aggressive characteristics.
Accordingly, there exists a significant need for a reliable marker based analysis useful in the prognosis of human mammary and other carcinomas, as well as in the characterization of subclasses of normal epithelial cells in tissue culture. The present invention fulfills these needs.